HOX genes are implicated in hematopoiesis and leukemogenesis based on their expression patterns in hematopoietic cell lines and their involvement in translocation events associated with leukemias. Their roles in these processes, however, are not well understood. In order to gain insights into the roles of HOX genes in normal hematopoiesis and AML progression, I propose to elucidate the expression patterns of HOX genes in immature and mature populations of hematopoietic progenitors, to engraft SCID mice with mature normal and AML cells overexpressing selected HOX genes, and block the transcription of HOX target genes to decipher their downstream signaling patterns.